VU0463271 quarterhydrate 

VU0463271 quarterhydrate is a potent KCC2 antagonist, with an IC₅₀ of 61 nM^[1].

IC50: 61 nM (KCC2)^[1].

VU0463271 is a potent antagonist of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC₅₀ of 61 nM and >100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters. It is also found rapidly cleared in vitro^[1].
VU0463271 is applied to the transected CNS preparation and resulted in a significant increase in firing rates of the Drosophila CNS with 1 μM VU0463271 resulting in a peak firing rate that was a 2.7- and 2.5-fold increase over baseline firing rate for OR and rdl strains, respectively^[2].
VU0463271 (10-100 nM) results in approximately 20% reduction of CNS firing frequency within a small percentage of preparations^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

VU0463271 is found to be a moderate-to-high clearance compound in rat (CL=57 mL/min/kg) following intravenous administration (1 mg/kg); the low volume of distribution at steady state (Vss 0.4 L/kg), coupled with moderate-to-high clearance produce a relatively short t1/2 (9 min) in vivo^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

387.00

C₁₉H₁₈N₄OS₂.1/4H₂O

Solid

Light yellow to yellow

O=C(N(C1CC1)C2=NC(C)=CS2)CSC3=NN=C(C4=CC=CC=C4)C=C3.[1/4].O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Delpire E, et al. Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: development of a highly selective and more potent in vitro probe. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4532-5.  [Content Brief]

  [2]. Rui Chen, et al. Functional Coupling of K +-Cl - Cotransporter (KCC) to GABA-Gated Cl - Channels in the Central Nervous System of Drosophila melanogaster Leads to Altered Drug Sensitivities. ACS Chem Neurosci. 2019 Jun 19;10(6):2765-2776.  [Content Brief]